EP0039091B1 - Spirobenzofuranon-Verbindungen - Google Patents

Spirobenzofuranon-Verbindungen Download PDF

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Publication number
EP0039091B1
EP0039091B1 EP81104399A EP81104399A EP0039091B1 EP 0039091 B1 EP0039091 B1 EP 0039091B1 EP 81104399 A EP81104399 A EP 81104399A EP 81104399 A EP81104399 A EP 81104399A EP 0039091 B1 EP0039091 B1 EP 0039091B1
Authority
EP
European Patent Office
Prior art keywords
compound
spirobenzofuranone
cyclopropane
furan
benzo
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired
Application number
EP81104399A
Other languages
English (en)
French (fr)
Other versions
EP0039091A1 (de
Inventor
Hirosada Sugihara
Masazumi Watanabe
Mitsuru Kawada
Isuke Imada
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Takeda Pharmaceutical Co Ltd
Original Assignee
Takeda Chemical Industries Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from JP5508279A external-priority patent/JPS55147271A/ja
Priority claimed from JP8055179A external-priority patent/JPS5931511B2/ja
Application filed by Takeda Chemical Industries Ltd filed Critical Takeda Chemical Industries Ltd
Publication of EP0039091A1 publication Critical patent/EP0039091A1/de
Application granted granted Critical
Publication of EP0039091B1 publication Critical patent/EP0039091B1/de
Expired legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/26—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D307/30—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D307/32—Oxygen atoms
    • C07D307/33—Oxygen atoms in position 2, the oxygen atom being in its keto or unsubstituted enol form
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/94—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom spiro-condensed with carbocyclic rings or ring systems, e.g. griseofulvins
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/10—Spiro-condensed systems

Definitions

  • This invention relates to spirobenzofuranone compounds, a process for their preparation, and the use of the said compounds.
  • the present spiro compounds have the following formula (I):
  • the 1-hydroxyethyl group is preferably present at the 5- or 7- position.
  • the compound (I) of the present invention can be produced, for example, by subjecting a compound of the formula (III): to reduction.
  • the reduction is carried out by treating a compound (II) with sodium borohydride in a suitable solvent under mild conditions which do not attack the 3-carbonyl group.
  • the compounds of this invention are of value as antiulcer, antiinflammatory and analgesic agents, and as drugs for the management of peptic ulcer, acute or chronic gastritis, lumbago, arthritis and other diseases.
  • Management of a peptic ulcer in accordance with the present invention includes both the prophylactic administration of the spiro compounds (I) to prevent the outbreak of an ulcer in an ulcer prone patient, as well as the treatment of an existing peptic ulcer.
  • each compound (I) can be safely administered orally or parenterally, either as it is or as formulated with pharmaceutically acceptable carriers of diluents known per se into suitable dosage forms such as tablets, powders, capsules, injections and suppositories.
  • the normal oral dosage for the treatment of peptic ulcer or acute or chronic gastritis is about 1 mg to 20 mg. as compound (I) per kg body weight per dose, to be given once to 3 times daily.
  • the starting compound (II) which is employed in the practice of this invention can be prepared by the procedure described in European Patent Publication No. 3084 published on July 25, 1979, or any process analogous thereto.
  • NaBH 4 (0.9 g) was added portionwise to a well stirred solution of 5-acetylspiro[benzo[b]furan-2(3H), 1'-cyclopropane]-3-one (1 g) in tetrahydrofuran (25 ml) and isopropanol (3 ml) with cooling at -50°C. The reaction mixture was then stirred at room temperature for 30 minutes, followed by dilution with ice-water, which was neutralized with aqueous ammonium chloride. The aqueous solution was extracted with ethyl acetate.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Claims (6)

1. Spirobenzofuranon-Verbindung der Formel
Figure imgb0010
2. Verbindung nach Anspruch 1, die 5-(1-Hydroxyethyl)spiro[benzo[b]furan-2(3H),1'cyclo- propan]-3-on ist.
3. Verbindung nach Anspruch 1, die 7-(1-Hydroxyethyl)spiro[benzo[b]furan-2(3H).1'cyclo- propan]-3-on ist.
4. Pharmazeutische Zusammensetzung, enthaltend als Wirkstoff eine wirksame Menge der Verbindung nach irgendeinem der Ansprüche 1 bis 3 und ein pharmazeutisch unbedenkliches Trägermaterial oder Verdünnungsmittel für diese.
5. Verbindung nach irgendeinem der Ansprüche 1 bis 3 oder pharmazeutische Zusammensetzung nach Anspruch 4 zur Verwendung bei der therapeutischen Behandlung von Säugern.
6. Verfahren zur Herstellung einer Spirobenzofuranon-Verbindung nach irgendeinem der Ansprüche 1 bis 3, dadurch gekennzeichnet, daß eine Verbindung der Formel
Figure imgb0011
einer Reduktion unterworfen wird.
EP81104399A 1979-05-04 1980-05-01 Spirobenzofuranon-Verbindungen Expired EP0039091B1 (de)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
JP55082/79 1979-05-04
JP5508279A JPS55147271A (en) 1979-05-04 1979-05-04 Spiro compound and its preparation
JP8055179A JPS5931511B2 (ja) 1979-06-25 1979-06-25 スピロ化合物およびその製造方法
JP80551/79 1979-06-25

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
EP80301431.5 Division 1980-05-01

Publications (2)

Publication Number Publication Date
EP0039091A1 EP0039091A1 (de) 1981-11-04
EP0039091B1 true EP0039091B1 (de) 1984-05-30

Family

ID=26395929

Family Applications (3)

Application Number Title Priority Date Filing Date
EP81104399A Expired EP0039091B1 (de) 1979-05-04 1980-05-01 Spirobenzofuranon-Verbindungen
EP81104398A Expired EP0038576B1 (de) 1979-05-04 1980-05-01 7-Acetylspirobenzofuranon-Verbindung
EP80301431A Expired EP0018830B1 (de) 1979-05-04 1980-05-01 Spiro-benzofuranon-Derivate, ihre Herstellung und sie enthaltende pharmazeutische Zusammensetzungen

Family Applications After (2)

Application Number Title Priority Date Filing Date
EP81104398A Expired EP0038576B1 (de) 1979-05-04 1980-05-01 7-Acetylspirobenzofuranon-Verbindung
EP80301431A Expired EP0018830B1 (de) 1979-05-04 1980-05-01 Spiro-benzofuranon-Derivate, ihre Herstellung und sie enthaltende pharmazeutische Zusammensetzungen

Country Status (10)

Country Link
EP (3) EP0039091B1 (de)
AT (1) AT383122B (de)
AU (1) AU534940B2 (de)
CA (3) CA1150287A (de)
DE (1) DE3063660D1 (de)
DK (1) DK153551C (de)
ES (4) ES8104996A1 (de)
GR (1) GR66729B (de)
NO (1) NO155053C (de)
SU (1) SU1022658A3 (de)

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK149891C (da) * 1977-12-27 1987-06-15 Takeda Chemical Industries Ltd Analogifremgangsmaade til fremstilling af spirobenzofuranon-forbindelser eller salte deraf med uorganiske eller organiske syrer eller alkalimetaller

Also Published As

Publication number Publication date
DE3063660D1 (en) 1983-07-14
ATA233880A (de) 1986-10-15
NO801290L (no) 1980-11-05
ES8205405A1 (es) 1982-06-01
EP0039091A1 (de) 1981-11-04
ES8203874A1 (es) 1982-04-01
ES491150A0 (es) 1981-05-16
EP0018830B1 (de) 1983-06-08
ES497669A0 (es) 1982-06-01
SU1022658A3 (ru) 1983-06-07
EP0018830A2 (de) 1980-11-12
AT383122B (de) 1987-05-25
CA1150287A (en) 1983-07-19
EP0038576B1 (de) 1984-04-11
AU5790380A (en) 1980-11-06
DK153551B (da) 1988-07-25
DK184680A (da) 1980-11-05
EP0038576A3 (en) 1981-11-18
CA1140562A (en) 1983-02-01
GR66729B (de) 1981-04-17
EP0038576A2 (de) 1981-10-28
ES8104996A1 (es) 1981-05-16
ES502179A0 (es) 1982-04-01
ES8203873A1 (es) 1982-04-01
EP0018830A3 (en) 1980-12-10
NO155053C (no) 1987-02-04
CA1138469A (en) 1982-12-28
ES502178A0 (es) 1982-04-01
NO155053B (no) 1986-10-27
DK153551C (da) 1988-12-05
AU534940B2 (en) 1984-02-23

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